The principal object of the proposed study is to evaluate the role of DNA repair during the initiation of hepatocarcinogenesis. First, I propose to carry out a quantitative comparison of the amount of DNA repair occurring in vivo in liver parenchymal cells of rats fed either 3'methyl-4-dimethylaminoazobenzene, 2-methyl-4-dimethylaminoazobenzene or 2-acetylaminofluorene for short periods of time. The amount of repair will be determined by measuring DNA repair-replication by the use of 5-bromodeoxyuridine. Alkaline sucrose gradient centrifugation will also be employed to characterize the effects of these three carcinogens on DNA structure and its subsequent repair. Second, I propose to determine the types of DNA repair mechanisms present in "adult" rat-liver-parenchymal-cells in primary monolayer culture and to compare them quantitatively with those found in various cell lines. As in the in vivo studies, DNA repair in vitro will also be monitored by measuring repair replication and using alkaline sucrose gradient centrifugation. In addition, since UV-irradiation will also be employed, DNA repair in this case will be followed by quantitating thymidine-dimer excision. These studies will yield important new information concerning both the actual DNA repair capacity of liver parenchymal cells in vitro compared to other types of cells and the actual amount of repair occurring in vivo during the initiation of carcinogenesis. The results obtained should further our understanding of the role of DNA repair in hepatocarcinogenesis.